Prostaglandin Fever in Rats Throughout the Estrous Cycle Late Pregnancy and Post Parturition

Abstract

We have examined the influence of natural variations in endocrine status on the ability to generate a prostaglandin-induced fever in virgin female, pregnant and lactating rats and compared responses to those in male rats. Endocrine status of virgin female rats was assessed from examination of vaginal smears and time of parturition noted to enable accurate dating of pre- and postparturient fevers. Unanesthetized rats, previously prepared with intraventricular guide cannulas and intraperitoneal telemetry thermistors, were given intraventricular injections of prostaglandin E1 (2-100 ng/5 microliters) and temperatures monitored for 3 h after injection. Virgin females developed significantly larger fevers than did males at higher doses. There were no significant alterations in either fever height or duration as a function of the phase of the reproductive cycle in the females. Both pregnant and postparturient rats within the several days around birth displayed significantly lower fevers than did virgin females, but there was no further reduction in the immediate periparturient period. These data indicate that there are sex-, and possibly hormone-dependent differences in the central mechanisms involved in fever generation and antipyresis.

Temporal Analysis of Lipopolysaccharide-Induced Sickness Behavior in Virgin and Lactating Female Rats

“…These authors proposed that the differential fever response was mainly linked to ovarian hormone levels because bilaterally ovariectomized females supplemented with sequential injections of estradiol-17β and progesterone exhibited significantly higher IL-1β-induced fever than ovariectomized rats that received estradiol-17β only. However, Martin et al [14] did not observe differences in LPS-induced fever as a function of the phase of the reproductive cycle in female rats.…”

“…The suppression of fever at term may be important for the health of the neonate because fever in pregnant mothers may be harmful to late-term fetuses and neonates [7,33]. Martin et al [14] showed that both pregnant and postparturient rats within several days after birth displayed significantly lower fevers than virgin females, but no further reduction was observed during the immediate periparturient period. They suggested that hormone-dependent differences may exist in the central mechanisms involved in fever generation and antipyresis.…”

“…The estrous phase was chosen to standardize the female hormonal status. No significant alterations in either fever magnitude or duration were found as a function of the phase of the reproductive cycle in female rats [14]. The control group consisted of virgin and lactating female rats treated with saline.…”

Fever suppression in near-term pregnant rats is dissociated from LPS-activated signaling pathways

“…It is well established that the febrile response to various pathogens is suppressed in pregnant animals at near term (10,36,42,43,69). However, the mechanisms that underlie this suppressed neuroimmune response are still elusive (10,12,17,18).…”

Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus

“…An absent or reduced fever has been observed in pregnant animals at near term (14) and, in some circumstances, is associated with abortion or mortality (23). This febrile refractoriness has been observed in many species, including guinea pig (55), rabbits (28), sheep (14), and rats (7,23,24), and has been observed in response to both peripherally injected pyrogens (14, 23, 55) and, to a lesser extent, to centrally infused prostaglandins (7,24,48). The fact that fever suppression is most dramatic in response to systemically administered LPS suggests that several steps in the cascade of responses to peripherally injected LPS may be affected.…”